Type 1 Diabetes Associated With Chronic Liver Disease
BOSTON — Patients with type 1 diabetes displayed a greater risk for developing chronic liver disease, including a fourfold prevalence for cirrhosis, compared with the general population, according to study data presented at The Liver Meeting. Among a longitudinal cohort of 4,644 patients with type 1 diabetes, researchers in the United Kingdom used a computer database to identify 57 (1.2%) who had undergone 82 liver biopsies. Each was gender-matched with insulin-treated (n=57) and noninsulin-treated type 2 diabetes patients (n=57). Both type 2 diabetes groups also had undergone liver biopsy. In the type 2 diabetes cohort (n=9,571), 270 patients (2.8%) underwent 301 liver biopsies. Compared with both type 2 diabetes arms, type 1 diabetes patients had lower occurrence of nonalcoholic fatty liver disease (OR=0.35; 95% CI, 0.15-0.82), but they showed higher diagnoses of glycogenosis (OR=9.1; 95% CI, 1.10-75.75). Researchers said 14 type 1 diabetes patients were diagnosed with cirrhosis during follow-up, which equated to a prevalence of at least 301.5 (170-520) per 100,000 individuals compared with an estimated cirrhosis prevalence of 76.3/100,000 (OR=3.96; 95% CI, 2.24-7.01) in the general UK population. Type 1 diabetes patients displayed a lower diagnosis rate of cirrhosis than type 2 diabetes patients using insulin (OR=0.46; 95% CI, 0.23-0.91) and type 2 nonusers (OR=0.42; 95% CI, 0.21-0.84). Twenty-two type 1 diabetes patients (38.6%) who had liver biopsy died during follow-up, which equated to an estimated crude death rate of 6,539/100,000 person-years, compared with an anticipated 1,878/100,000 person-years based on the National Diabetes Mortality Analysis 2007-08. “A patient with type 1 diabetes is at a significant risk of developing liver disease, and I don’t th Continue reading >>
Non-alcoholic Fatty Liver Disease And Diabetes
Abstract Non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM) are common conditions that regularly co-exist and can act synergistically to drive adverse outcomes. The presence of both NAFLD and T2DM increases the likelihood of the development of complications of diabetes (including both macro- and micro- vascular complications) as well as augmenting the risk of more severe NAFLD, including cirrhosis, hepatocellular carcinoma and death. The mainstay of NAFLD management is currently to reduce modifiable metabolic risk. Achieving good glycaemic control and optimising weight loss are pivotal to restricting disease progression. Once cirrhosis has developed, it is necessary to screen for complications and minimise the risk of hepatic decompensation. Therapeutic disease modifying options for patients with NAFLD are currently limited. When diabetes and NAFLD co-exist, there are published data that can help inform the clinician as to the most appropriate oral hypoglycaemic agent or injectable therapy that may improve NAFLD, however most of these data are drawn from observations in retrospective series and there is a paucity of well-designed randomised double blind placebo controlled studies with gold-standard end-points. Furthermore, given the heterogeneity of inclusion criteria and primary outcomes, as well as duration of follow-up, it is difficult to draw robust conclusions that are applicable across the entire spectrum of NAFLD and diabetes. In this review, we have summarised and critically evaluated the available data, with the aim of helping to inform the reader as to the most pertinent issues when managing patients with co-existent NAFLD and T2DM. Continue reading >>
Nonalcoholic Fatty Liver Disease And Chronic Vascular Complications Of Diabetes Mellitus
Nonalcoholic fatty liver disease and chronic vascular complications of diabetes mellitus Nature Reviews Endocrinology volume 14, pages 99114 (2018) Nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus are common diseases that often coexist and might act synergistically to increase the risk of hepatic and extra-hepatic clinical outcomes. NAFLD affects up to 7080% of patients with type 2 diabetes mellitus and up to 3040% of adults with type 1 diabetes mellitus. The coexistence of NAFLD and diabetes mellitus increases the risk of developing not only the more severe forms of NAFLD but also chronic vascular complications of diabetes mellitus. Indeed, substantial evidence links NAFLD with an increased risk of developing cardiovascular disease and other cardiac and arrhythmic complications in patients with type 1 diabetes mellitus or type 2 diabetes mellitus. NAFLD is also associated with an increased risk of developing microvascular diabetic complications, especially chronic kidney disease. This Review focuses on the strong association between NAFLD and the risk of chronic vascular complications in patients with type 1 diabetes mellitus or type 2 diabetes mellitus, thereby promoting an increased awareness of the extra-hepatic implications of this increasingly prevalent and burdensome liver disease. We also discuss the putative underlying mechanisms by which NAFLD contributes to vascular diseases, as well as the emerging role of changes in the gut microbiota (dysbiosis) in the pathogenesis of NAFLD and associated vascular diseases. Subscribe to Nature Reviews Endocrinology for full access: European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD) & European Association for the Study of Obesity (EASO). EASL-EASD-EAS Continue reading >>
Why You Should Know About Fatty Liver Disease
Non-alcoholic fatty liver disease can be a problem for people with diabetes, especially type 2 diabetes. Learn more about this growing condition. Fatty liver disease is an “underappreciated problem that seems to be getting worse,” according to Mitch Lazar, MD, PhD, chief of the division of endocrinology, diabetes and metabolism at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia. For many years physicians believed that fatty liver was a benign condition but in 1980 non-alcoholic fatty liver disease (NAFLD) was designated a real condition. “Fortunately with increasing knowledge and research on the disease, there is a growing awareness,” says Dina Halegoua-Demarzio, MD, director of the Fatty Liver Center at Thomas Jefferson University Hospital, also located in Philadelphia. “More awareness of the problem in doctors and patients will enable early intervention that can prevent cirrhosis, liver failure and liver cancer.” It’s a particular issue for people with type 2 diabetes. Up to 70 percent of obese type 2 diabetes patients have fatty livers, meaning at least five percent of liver cells show evidence of fat. Although fatty livers are benign and estimates vary considerably, about five to 10 percent of people with the condition will go on to develop the more serious non-alcoholic steatohepatitis (NASH) that causes inflammation, scarring and damage to the liver cells. 1 Fatty livers can also start a cascade of serious damage to the liver and attempts by the organ to regenerate itself that culminate in an abundance of scar tissue and impaired liver function. It has also been linked to increased risk of heart attack and stroke.2 Studies show that anywhere from three to 26 percent of people with NASH will progress to cirrhosis, whi Continue reading >>
Prevalence Of Hepatopathy In Type 1 Diabetic Children
Abstract The Prevalence of liver disease among diabetics has been estimated to be between 17% and 100%. Most of these data were obtained from adult studies. The aim of our study was to screen for liver disease among type 1 diabetic children. Methods Children with type 1 diabetes following in clinic have been examined for existence of liver disease, from November 2008 to November 2009. All were subjected to the following: History, physical examination, liver function tests, fasting lipid profile, HbA1C, and ultrasound of the liver. A hyperechogenic liver and/or hepatomegaly on ultrasound were attributed most likely to excess glycogen or fat in the liver, after negative extensive work-up to rule out other underlying liver disease. 106 children with type 1 diabetes were studied: age ranged between 8 months to 15.5 years, sixty two patients were females. Twenty two patients (21%) were identified to have abnormal findings on ultrasound of the liver: 10 patients had hepatomegaly and 12 had hyperechogenic liver. The group with hyperechogenic liver had poorer glycemic control than patients with normal liver (Mean HbA1c 12.14% Vs 10.7%; P value = 0.09). Hyperechogenic liver resolved in 60% at 6 months follow-up upon achieving better glycemic control. Hyperechogenic liver and/or hepatomegaly are not uncommon in children with type 1 diabetes and tend to be more prevalent among children with poor glycemic control. Type 1 diabetes related hepatopathy is reversible by optimizing glycemic control. Because of its safety, and reliability, ultrasound can be used to screen for hepatopathy in type 1 diabetic child. Background Type 1 diabetes is a disorder of glucose metabolism that results from insulin deficiency secondary to autoimmune destruction of insulin-secreting β-cells. The preval Continue reading >>
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The Role Of The Liver In Type 1 Diabetes
In part one of this exclusive interview, Dr. Robert Geho discusses the essential role of the liver in metabolizing insulin, and asks why we hear about the artificial pancreas all the time, but never hear anyone talk about an artificial liver? To view this interview as a video, click here. Steve Freed: This is Steve Freed with Diabetes in Control and we’re here in the Boston, Diabetes Symposium 2016. We have a lot of companies, new products and some great ideas. Today we have a special guest, Dr. Robert Geho. I think I’ll let him introduce himself. He’s the CEO of a company, he works with a number of groups. So why don’t you start and tell us a little bit about yourself and what you do. Robert Geho: Thank you, Steve, for the invitation to speak with you. As you mentioned I am the CEO of a company called Diasome Pharmaceuticals, which is based in Cleveland, Ohio. We are focused on using a novel globally patented drug delivery system to specifically deliver insulin molecules that are currently sold as commercial insulins from the big three insulin manufacturers to cells in the liver called hepatocytes. Hepatocytes are the major metabolic cells in the liver. They are responsible for managing, storing and then releasing up to 2/3rds of all the sugar that a person eats during the meal. They will only do that if they are getting the insulin signal, which is very difficult to have happen with current injective insulin. So Diasome is a phase 3 enabled technology company, which means the FDA has given us clearance to go into phase 3 with our material, which we call HDV, which stands for Hepatocyte Directed Vesicles. It can be added to any commercial form of insulin. We are embarking shortly, dosing the first patient in a 200 subject, all type 1s Phase 2b study. So it’s Continue reading >>
Diabetes And Nonalcoholic Fatty Liver Disease: A Pathogenic Duo
Limitation of Use: The safety and efficacy of Humulin R U-500 used in combination with other insulins has not been determined. The safety and efficacy of Humulin R U-500 delivered by continuous subcutaneous infusion has not been determined. For the Humulin R U-500 vial, particular attention should be paid to the 20-mL vial size, prominent “U-500” and warning statements on the vial label, and distinctive coloring on the vial and carton. Dosing errors have occurred when Humulin R U-500 was administered with syringes other than a U-500 insulin syringe. Patients should be prescribed U-500 syringes for use with Humulin R U-500 vials. The dose of Humulin R U-500 should always be expressed in units of insulin. DO NOT transfer Humulin R U-500 from the Humulin R U-500 KwikPen into any syringe for administration. Overdose and severe hypoglycemia can occur. Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Changes in insulin, manufacturer, type, or method of administration should be made cautiously and only under medical supervision and the frequency of blood glucose monitoring should be increased. Hypoglycemia: Hypoglycemia is the most common adverse reaction associated with insulin, including Humulin R U-500. Severe hypoglycemia can cause seizures, may be life-threatening, or cause death. Severe hypoglycemia may develop as long as 18 to 24 hours after an injection of Humulin R U-500. Hypoglycemia can impair concentration ability and reaction time; this may place an individual and others at risk in situations where these abilities are important, such as driving or operating other machinery. Early warning symptoms of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic nerve disease, in patients using medications th Continue reading >>
Spectrum Of Liver Disease In Type 2 Diabetes And Management Of Patients With Diabetes And Liver Disease
It is estimated that 20.8 million people, i.e., 7.0% of the U.S. population, have diabetes (1). Type 2 diabetes, with its core defects of insulin resistance and relative insulin deficiency, accounts for 90–95% of those with the disease. Another 5.2 million people are estimated to have undiagnosed type 2 diabetes. It is the sixth leading cause of death (1) in the U.S. and accounts for 17.2% of all deaths for those aged >25 years (2). Liver disease is an important cause of death in type 2 diabetes. In the population-based Verona Diabetes Study (3), cirrhosis was the fourth leading cause of death and accounted for 4.4% of diabetes-related deaths. The standardized mortality ratio (SMR), i.e., the relative rate of an event compared with the background rate, for cirrhosis was 2.52 compared with 1.34 for cardiovascular disease (CVD). In another prospective cohort study (4), cirrhosis accounted for 12.5% of deaths in patients with diabetes. Diabetes, by most estimates, is now the most common cause of liver disease in the U.S. Cryptogenic cirrhosis, of which diabetes is, by far, the most common cause, has become the third leading indication for liver transplantation in the U.S. (5,6). Virtually the entire spectrum of liver disease is seen in patients with type 2 diabetes. This includes abnormal liver enzymes, nonalcoholic fatty liver disease (NAFLD), cirrhosis, hepatocellular carcinoma, and acute liver failure. In addition, there is an unexplained association of diabetes with hepatitis C. Finally, the prevalence of diabetes in cirrhosis is 12.3–57% (7). Thus, patients with diabetes have a high prevalence of liver disease and patients with liver disease have a high prevalence of diabetes. The management of diabetes in patients with liver disease is theoretically complicated b Continue reading >>
What Every Diabetic Should Know About Liver Disease
What Every Diabetic Should Know About Liver Disease Did you know that diabetics are 50% more likely to develop liver disease? Particularly fatty liver disease. Fatty liver disease is incredibly common in overweight people; nearly everyone with excess weight on their abdomen has some degree of fatty liver. Type 2 diabetics are prone to carrying excess weight on their abdomen, but even slim diabetics often have a fatty liver. It is well known that diabetes increases the risk of kidney disease, nerve damage, blood vessel damage, infections, blindness, erectile problems and heart disease, but you may not realise diabetes has terrible effects on the liver. You can’t see or feel the effects it’s having on your liver until liver cells become damaged. According to Gillian Booth, MD, MSc, of St. Michael’s Hospital in Toronto, in a population-based study, newly diagnosed diabetes was linked with a near doubling in the rate of cirrhosis, liver failure or liver transplant compared with non-diabetics. Clearly these are significant findings that should be taken seriously. Insulin resistance (syndrome X) is the driving force behind the development of fatty liver. Insulin resistance is a forerunner to type 2 diabetes. If the insulin resistance becomes severe enough, a person usually develops type 2 diabetes. Type 1 diabetes usually develops in childhood, although by the time they are in their mid 30s, most type 1 diabetics have developed insulin resistance as well, and they face the same risks as type 2 diabetics when they get older. People with insulin resistance have high levels of insulin in their bloodstream. Insulin signals to your liver to manufacture fat, especially triglycerides and cholesterol. This promotes the accumulation of fat inside the liver, inside other organs, Continue reading >>
Glycogenic Hepatopathy In Type 1 Diabetes Mellitus
Copyright © 2015 Murat Atmaca et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Glycogenic hepatopathy is a rare cause of high transaminase levels in type 1 diabetes mellitus. This condition, characterized by elevated liver enzymes and hepatomegaly, is caused by irreversible and excessive accumulation of glycogen in hepatocytes. This is a case report on a 19-year-old male case, diagnosed with glycogenic hepatopathy. After the diagnosis was documented by liver biopsy, the case was put on glycemic control which led to significant decline in hepatomegaly and liver enzymes. It was emphasized that, in type 1 diabetes mellitus cases, hepatopathy should also be considered in the differential diagnoses of elevated liver enzyme and hepatomegaly. 1. Introduction Liver enzyme elevation is more common among diabetic patients compared to the general population. This condition is often associated with nonalcoholic hepatosteatosis [1, 2]. Another very rare cause of elevated liver enzymes, especially among type 1 diabetic patients, is glycogenic hepatopathy (GH). GH develops due to excessive and irreversible accumulation of glycogen in the hepatocytes and causes liver function disorders and hepatomegaly [3, 4]. Mauriac first defined GH in a child with brittle diabetes, as a component of Mauriac syndrome, characterized by delayed development, hepatomegaly, cushingoid appearance, and delayed puberty [5]. Additionally, GH can also be observed in adult type 1 diabetic individuals without other components of Mauriac syndrome [6–8]. Hyperglycemia and overinsulinization (poor glycemic control) are believed to be Continue reading >>
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The Liver And Diabetes
Tweet The liver is one of the most important organs in our bodies, playing a central role in a number of important processes. One of these is to help control glucose concentration in the blood (i.e. regulating blood glucose levels). A healthy liver helps keep blood glucose within the ‘normal range’ and protects against excessive fluctuations, which is vital as high blood sugar (hyperglycemia) and low blood sugar (hypoglycemia) can both be dangerous for the human body. What is the liver? The liver is the largest internal organ of the human body, weighing approximately 1.4 kg (3 lb) in the average adult. Located under your diaphragm (more to the right side of your body), it is a wedge-shaped, spongy organ that performs a number of key functions, including regulating blood sugar levels, getting rid of toxins (body detoxification) and bile production. It also acts as a major filter of the blood travelling from the digestive tract to the rest of the body. The liver’s response to stress The body responds to stress by releasing hormones from the adrenal glands within the kidneys. These hormones travel within the blood to the liver and trigger the liver to release some of its stored glycogen. Release of glucose into the blood is part of the body’s ‘fight or flight’ response, preparing the body with energy to be able to quickly respond to a threat or stressful situation. Read more on stress and blood glucose levels The liver’s response to exercise During exercise, or other forms of physical activity, the liver plays a part in regulating blood glucose levels. When you begin physical activity, glycogen from the muscles are mobilised to be used as a source of fuel. As glucose is taken up by the muscles, the liver releases glucose into the blood. The liver can only sto Continue reading >>
Liver Disease And Diabetes Mellitus
CLINICAL DIABETES VOL. 17 NO. 2 1999 These pages are best viewed with Netscape version 3.0 or higher or Internet Explorer version 3.0 or higher. When viewed with other browsers, some characters or attributes may not be rendered correctly. FEATURE ARTICLE Gavin N. Levinthal, MD, and Anthony S. Tavill, MD, FRCP, FACP IN BRIEF Liver disease may cause or contribute to, be coincident with, or occur as a result of diabetes mellitus. This article addresses these associations. This article addresses the role of the liver in normal glucose homeostasis and discusses a variety of liver conditions associated with abnormal glucose homeostasis. This association may explain the pathogenesis of the liver disease or of the abnormal glucose homeostasis, or may be purely coincidental (Table 1). Table 1. Liver Disease and Diabetes Mellitus 1. Liver disease occurring as a consequence of diabetes mellitus Glycogen deposition Steatosis and nonalcoholic steatohepatitis (NASH) Fibrosis and cirrhosis Biliary disease, cholelithiasis, cholecystitis Complications of therapy of diabetes (cholestatic and necroinflammatory) 2 . Diabetes mellitus and abnormalities of glucose homeostasis occurring as a complication of liver disease Hepatitis Cirrhosis Hepatocellular carcinoma Fulminant hepatic failure Postorthotopic liver transplantation 3 . Liver disease occurring coincidentally with diabetes mellitus and abnormalities of glucose homeostasis Hemochromatosis Glycogen storage diseases Autoimmunebiliary disease The prevalence of type 1 diabetes in the United States is ~0.26%. The prevalence of type 2 diabetes is far higher, ~1–2% in Caucasian Americans and up to 40% in Pima Indians. According to the Centers for Disease Control and Prevention, hepatitis C alone chronically infects more than 1.8% of the A Continue reading >>
Type 1 Diabetes And Non-alcoholic Fatty Liver Disease: When Should We Be Concerned? A Nationwide Study In Brazil †
Go to: 2. Materials and Methods This was a cross-sectional study, based in a multicenter cohort of T1D patients, evaluated between August 2011 and August 2014 at 14 public clinics of secondary and tertiary care, located in 10 cities in all Brazilian geographic regions (North/Northeast, Midwest, Southeast, and South). The methods have been described previously [21]. Briefly, all patients attended secondary and tertiary clinics from the National Brazilian Health Care System and were seen by an endocrinologist. They had access to free neutral protamine Hagedorn (NPH) and regular insulin, syringes, needles, glucometers, and strips for blood glucose monitoring. The inclusion criteria were: patients were older than or equal to 13 years of age, diagnosed by a physician with T1D through classical clinical findings (hyperglycemia, polyuria, weight loss, polydipsia, polyphagia, and the need for insulin therapy since diagnosis), and had attended medical follow-up for at least six months in each center. The exclusion criteria included: being pregnant or breastfeeding at the time of inclusion; acute infectious process or history of ketoacidosis in the three months prior to recruitment; or exacerbation of comorbidities, such as congestive heart failure, cardiac arrhythmias, acute respiratory failure, or severe obstructive lung disease at the time of enrollment. Each center provided data for at least 50 T1D patients, which were analyzed by a trained coordinator. Participants underwent a clinical-demographic survey by a standardized questionnaire in which data were collected on gender, current age, self-reported ethnicity, age at diagnosis, as well as diabetes duration, diet (characteristics and adhesion in last month), level of physical activity, smoking (defined as the current use of Continue reading >>
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Diabetes: How Do I Help Protect My Liver?
If I have diabetes, is there anything special I need to do to take care of my liver? Answers from M. Regina Castro, M.D. You're wise to wonder about steps to protect your liver. Diabetes raises your risk of nonalcoholic fatty liver disease, a condition in which excess fat builds up in your liver even if you drink little or no alcohol. This condition occurs in at least half of those with type 2 diabetes. It isn't clear whether the condition appears more often in people with type 1 diabetes than in the general population because obesity, which is a risk factor, occurs with similar frequency in both groups. Other medical conditions, such as high cholesterol and high blood pressure, also raise your risk of nonalcoholic fatty liver disease. Fatty liver disease itself usually causes no symptoms. But it raises your risk of developing liver inflammation or scarring (cirrhosis). It's also linked to an increased risk of liver cancer, heart disease and kidney disease. Fatty liver disease may even play a role in the development of type 2 diabetes. Once you have both conditions, poorly managed type 2 diabetes can make fatty liver disease worse. Your best defense against fatty liver disease includes these strategies: Work with your health care team to achieve good control of your blood sugar. Lose weight if you need to, and try to maintain a healthy weight. Take steps to reduce high blood pressure. Keep your low-density lipoprotein (LDL, or "bad") cholesterol and triglycerides — a type of blood fat — within recommended limits. Don't drink too much alcohol. If you have diabetes, your doctor may recommend an ultrasound examination of your liver when you're first diagnosed and regular follow-up blood tests to monitor your liver function. Continue reading >>
Fatty Liver Disease May Be Less Common In Type 1 Diabetes
Fatty Liver Disease May Be Less Common in Type 1 Diabetes Fatty Liver Disease May Be Less Common in Type 1 Diabetes Patients with type 1 diabetes may be protected from steatosis and hepatic insulin resistance, according to data published in the Journal of Clinical Endocrinology & Metabolism. Further, researchers found that, unlike in type 2 diabetes, obesity may not raise insulin requirements in type 1 diabetes. In this study, the researchers compared overweight adult patients with type 1 diabetes (n=32) with patients without diabetes (n=32). Patients were matched for age, BMI and gender. To measure liver fat content, the researchers used proton magnetic resonance spectroscopy. They also assessed body composition using MRI and insulin sensitivity using the euglycemic hyperinsulinemic clamp technique. Results revealed lower liver fat content in patients with type 1 diabetes vs. those without diabetes (P<.001). Additionally, the endogenous rate of glucose production during euglycemic hyperinsulinemia (P=.012) was significantly lower and the percent suppression of endogenous glucose production by insulin was significantly higher (P=.009) in patients with type 1 diabetes vs. those without diabetes. Data also indicated that patients with type 1 diabetes had significantly lower serum non-esterified fatty acid (NEFA) concentrations during euglycemic hyperinsulinemia and significantly higher percent suppression of NEFA (P<.001) than those without diabetes. The researchers reported that insulin doses were similar across BMI categories, according to the study. They concluded that their results suggest that patients with type 1 diabetes may be shielded from steatosis and its adverse metabolic consequences. BACKGROUND: Patients with type 1 diabetes (T1DM) lack the portal/periphera Continue reading >>
